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Biomedical subjects

C Cohen

Publications and source records attributed to C Cohen.

At least 289 records · Page 16Linked to original sources

Isolation and characterization of a lysine-specific protease from Pseudomonas aeruginosa.

We report here a procedure which results in the purification of an extracellular protease (designated Ps-1) from Pseudomonas aeruginosa. This enzyme cleaves fibrinogen so that the modified molecules form microcrystals and large single crystals. Precise knowledge of the Ps-1 cleavage sites is essential for the interpretation of the structural information provided by these crystals (Weisel, J. W., Stauffacher, C. V., Bullitt, E., and Cohen, C. (1985) Science 230, 1388-1391). Ps-1 is a single-chain polypeptide of Mr 30,000 which appears to function as a monomer. The pH optimum is 8-9. The activity of the protease is not decreased by inhibitors of thiol, carboxyl, or metallo proteases; the abolishment of activity by N alpha-p-tosyl-L-lysine chloromethyl ketone and the partial inhibition obtained with serine-reactive inhibitors suggests that Ps-1 may be a serine protease with an unusual active-site conformation. Studies with synthetic peptide substrates show that Ps-1 exhibits one of the most restricted specificities known for an endoproteinase: only peptide, ester, and amide bonds containing the carbonyl group of lysine are hydrolyzed. The limited specificity of Ps-1 should make it useful for other applications requiring the selective cleavage of proteins, such as sequence analysis and the isolation of domains.

Amino Acids↗

Porphobilinogen deaminase and the synthesis of porphyrin isomers in the Dubin-Johnson syndrome.

Porphyrin synthesis was studied in a family of 9.3 of whom had the Dubin-Johnson syndrome (DJS). Subjects with DJS had modest increases in urinary porphyrin concentration with a marked increase in the series I isomer of coproporphyrin (tetracarboxylic) as well as in the octa-, hepta-, hexa- and penta-carboxyl porphyrins. Activity of erythrocyte porphobilinogen deaminase (PBG-D) was also increased. Non-expressing carriers in the family had normal levels of urinary porphyrins but modest increases in both series I isomer accumulation and PBG-D activity. These results may provide a rationale for the altered synthesis of porphyrin in DJS.

Adolescent↗

Liver cell dysplasia in normal, cirrhotic, and hepatocellular carcinoma patients.

An assessment was made of the frequency of liver cell dysplasia and the mean age of each group in 56 normal, 13 cirrhotic, and 50 hepatocellular carcinoma (HCC) patients, 40 with cirrhosis, from southern Africa. Dysplasia increased from 7.1% in normal subjects to 38.5% in cirrhotic, 40% in noncirrhotic HCC, and 52.5% in cirrhotic HCC patients, three statistically similar frequencies. Average patient ages were as follows: patients with normal livers, 37.3 years; with cirrhosis, 42.4 years; with noncirrhotic HCC, 36.5 years; and with cirrhotic HCC, 34 years, the mean age with dysplasia being lower than that of the whole group. With no increase in frequency of dysplasia from cirrhosis to HCC with cirrhosis, with a similar high frequency in HCC without cirrhosis, and with a mean age of all HCC patients 8 years less than that of cirrhotics and 3 years less than normals, chronologic evolutionary progression from cirrhosis to dysplasia to HCC in southern Africa cannot be demonstrated.

Adult↗

Spontaneous breast infarction associated with pregnancy presenting as a palpable mass.

Spontaneous infarction of physiologically hyperplastic breast tissue or of an adenoma-fibroadenoma presenting as breast mass during pregnancy or in the early postpartum period is a recognized but rare clinical pathologic entity. Only 24 such cases have been reported in the English language literature to our knowledge. We report four additional cases of breast infarction associated with pregnancy, review the literature, and discuss possible etiologies and pathogenesis of this uncommon event.

Adolescent↗

Monoclonal antibodies for detection of lymphocyte markers: comparison of three commercial kits.

Three commercial monoclonal antibody kits (Histoset, OrthoDiagnostics, Raritan, NJ; T Cell Panel, Becton Dickinson, Mountain View, CA; Histotag Lymphoma Set, Hybritech Inc., San Diego, CA) were compared, using touch preparations, frozen sections, and formalin-fixed paraffin-embedded sections of 14 tonsils. With the first two kits, sensitive results were obtained in touch preparations and frozen sections with strong, crisp, reproducible immunostain. Results were accurate and easily interpreted despite moderate background staining. Distribution and numbers of lymphocytes and subsets were appropriate. The Histotag Lymphoma Set was sensitive for detection of T-cells in touch preparations and frozen sections. Hazy, moderate immunostain was obtained with B-cell and common leukocyte antibodies. Accuracy was questioned because of variable and false-negative results (75% in touch preparations) with all anti-sera, and interfollicular staining for B-lymphocytes. In formalin-fixed sections, positive results of low sensitivity were obtained only with the T Cell Panel. The Histoset and T Cell Panel are recommended, particularly for use with frozen sections.

Antibodies, Monoclonal↗

Multiple trichogenic adnexal tumors.

A young girl developed multiple generalized subcutaneous nodules and two polypoid ear lesions between birth and 8 years of age. There was no family history or evidence of systemic disease. The subcutaneous nodules were trichogenic myxomas, consisting of vascular myxoid connective tissue, sometimes with islands of stratified squamous epithelium, keratinous cysts of epidermal type, or dermoid cysts with follicular and/or sebaceous differentiation. The polypoid lesions were trichofolliculomas, with areas similar to trichogenic myxomas. Our patient thus has multiple trichogenic tumors, the majority being pure hamartomas of the dermal papilla (trichogenic myxomas), others being a combined trichogenic myxoma and hamartoma of hair germ (trichofolliculoma).

Adenoma↗

Fordyce's granules in the oral mucosa of adult Israeli Jews.

The prevalence of Fordyce's granules in a group of 2,462 Israeli Jews was determined. Fordyce's granules were observed in 94.9% of the entire sample. The most common location was the vermilion border of the upper lip (82.2%), followed by the retromolar area (73.3%), the buccal mucosa (65.9%) and the vermilion border of the lower lip (29.2%). The granules were common in men. A significant difference in prevalence was found between the Ashkenazi group and each of the other two ethnic groups.

Adolescent↗

Overestimation of infarct size by quantitative two-dimensional echocardiography: the role of tethering and of analytic procedures.

Analyses of regional left ventricular systolic wall motion or thickening overestimate infarct size. We used quantitative two-dimensional echocardiographic analysis of systolic thickening and contrast two-dimensional echocardiography to evaluate causes for that overestimation. The following possibilities were considered: "tethering," defined as dysfunction of contrast-enhancing myocardium adjacent to ischemic or contrast-negative regions, and the role of standard center of mass analysis algorithms, which may overestimate wall motion abnormalities because of the axis shift produced by simultaneous systolic expansion of the ischemic segment and systolic contraction of the nonischemic segment. In the short-axis view in 12 animals, the echo contrast defect (ECD) occupied 32 +/- 7% of the left ventricular circumference. Extent of dysfunction by the center of mass analysis was 39 +/- 5% of the left ventricular circumference and correlation with ECD size was .68 (SEE = 5.2%). Thus 8 +/- 6% of the circumference of the left ventricle was assessed to be dysfunctional yet enhanced with contrast. Tethering accounted for only half of this (4 +/- 4% of left ventricular circumference) and involved less than 1 cm on either side of the ECD. The remaining overestimation by the center of mass analysis correlated significantly (r = .89, p less than .01) with the amount of systolic expansion of the ECD. This expansion of the ECD (increase in angle subtended by the ECD of 11 +/- 8%) was produced by the systolic shift in the center of mass toward the dysfunctional segment from contraction of the opposite, nonischemic segment.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Measurability of non-small-cell lung cancer on chest radiographs.

Response rates to various drug regimens are determined in multi-center trials by radiographic measurement of tumor dimensions before and after treatment. The way in which lesions are measured may affect the reported results. Lesions due to primary lung cancer may be more difficult to assess than rounded peripheral metastases. No previous study has assessed the variability of tumor measurements in patients with primary lung cancer. Nineteen radiographs from 12 patients with non-small-cell lung cancer (NSCLC) were shown to 25 experienced readers on two separate occasions. Pre- and post-treatment (combined chemotherapy and radiotherapy) radiographs were first shown separately, unidentified and in random order. Three months later, they were shown side by side with the facility for comparison. A decrease in tumor size of greater than or equal to 50% was considered as a "response." Viewing paired films together increased the viewers ability to measure tumors compared with reading each film of the radiographic pair individually. Fifty-one percent of unmeasurable pairs became measurable when read together, whereas 13% of previously measurable pairs now became unmeasurable. The interobserver variation in measurements was 10% to 265%, while the intraobserver variation was 4% to 10%. The correlation between responses calculated on the first and second readings often was no better than chance alone. Subjective impressions of degree of improvement showed no good correlation with response rates measured objectively. Because of the large variation in measurements and consequently in response rate, we recommend that all radiographs be reviewed by a single observer for any particular study, and pre- and post-treatment radiographs be evaluated together.

Antineoplastic Combined Chemotherapy Protocols↗

A comparison of responses to albuterol delivered by two aerosol devices.

Nineteen outpatients with stable obstructive pulmonary disease (mean forced expiratory volume in one second [FEV1], 1.00 + 0.10 L) were evaluated for airway response to albuterol (salbutamol) administered by metered-dose inhaler and Bosch ultrasonic nebulizer (BUSN). Albuterol administered by metered-dose inhaler but not by nebulizer caused a significant increase in FEV1 and the mean forced expiratory flow over the middle half of the forced vital capacity (FEF25-75%) (p less than 0.02). Absolute increase from baseline of FEV1 and FEF25-75% was significantly greater for metered-dose inhaler (0.21 +/- 0.05 L; 0.32 +/- 0.13 L/sec) compared to ultrasonic nebulizer (0.07 +/- 0.03 L; 0.03 +/- 0.04 L/sec) (p less than 0.02). In 11 subjects (mean FEV1, 1.08 + 0.14 L), the placebo effect of inhalation of the diluent from the metered-dose inhaler (Freon) and the ultrasonic nebulizer (isotonic saline solution) was determined. Freon produced the mean increase of 1.5 percent, whereas the ultrasonic aerosol of isotonic saline solution resulted in a mean decrease of 8 percent in FEV1. Therefore, the inferior response to albuterol administered by ultrasonic nebulizer was at least in part due to the superimposed broncho-constriction occurring with ultrasonically administered saline solution. The metered-dose inhaler was more effective than the ultrasonic nebulizer for administration of albuterol in stable obstructive pulmonary disease, and the latter device is not recommended. A specific ultrasonic nebulizer should be prescribed only if its superiority to a metered-dose inhaler can be objectively documented.

Aerosols↗

A model for fibrinogen: domains and sequence.

Electron microscopy of rotary-shadowed fibrinogen demonstrates that the molecules modified for crystallization by limited cleavage with a bacterial protease retain the major features of the native structure. This evidence, together with image processing and x-ray analysis of the crystals and of fibrin, has been used to develop a three-dimensional low resolution model for the molecule. The data indicate that the two large end domains of the molecule would be composed of the carboxyl-terminus of the B beta chain (proximal) and gamma chain (distal), respectively; the carboxyl-terminus of the A alpha chain would fold back to form an additional central domain. On this basis, the carboxyl-terminal region of each of the three chains of fibrinogen is folded independently into a globular domain.

Amino Acid Sequence↗

Liver iron stores and hepatitis B antigen status.

Higher serum iron and ferritin levels noted in hepatitis B antigen (HBAg) carriers than in noncarriers suggests that virus might actively replicate in hepatocytes, stimulate ferritin synthesis, and result in increased liver iron stores. A comparative semiquantitative study of immunohistochemical ferritin (0-12) and hemosiderin (0-9) was performed on 54 normal, 13 cirrhotic, and 70 nonneoplastic livers from patients with hepatocellular carcinoma, in each group, comparing amounts in HBAg-positive and HBAg-negative patients. Mean scores for ferritin and hemosiderin were high in all three groups, normal livers averaging 8.3 and 6, respectively, cirrhotic livers, 8.5 and 7.4, respectively, and carcinoma livers, 5.6 and 6.1, respectively. In each group, there was no significant difference in ferritin and hemosiderin mean scores in HBAg-positive and HBAg-negative patients. The large liver iron stores do not appear to be a consequence of hepatitis B virus infection alone. Their role in the development of hepatocellular carcinoma is still to be elucidated.

Carcinoma, Hepatocellular↗

Electron microscopy of cross-linked scallop myosin.

The N-terminal regions of the regulatory light chains on the two heads of scallop myosin can be cross-linked to one another. Electron microscopy of cross-linked myosin molecules, and of dimers of myosin subfragment-1 produced by digesting them with papain, shows that the site of cross-linking is very close to the head-rod junction.

Animals↗

Neuromotor maturation and psychological performance: a developmental study.

Groups of 50 normal kindergarten and 50 first-grade children were examined three times at six-month intervals on the extended neuromotor examination for children, as well as on measures of reading achievement and language performance. The joint effect of five neuromotor measures accounted for a substantial percentage of variance in reading achievement and language performance 12 months later. As a global measure, neuromotor status therefore may constitute a reliable, independent criterion of developmental age for psychological investigations of young, normal children. The best individual predictors of psychological outcome were mirror movements and speed of timed motor repetitions, while reading achievement and automated naming speed were the dependent measures most closely associated over time with neuromotor status. Such findings suggest that the individual motor signs may also provide indirect clues about the presumed functional relationship between development of motor co-ordination and language competence.

Achievement↗

Commissural lip pits in Israeli Jews of different ethnic origin.

The prevalence of commissural lip pits in a group of 2462 Israeli Jews was determined, and a relation of commissural lip pits to ethnic background was noted. Results showed the presence of commissural lip pits in 17.4% of the entire sample; 9.7% were unilateral and 7.7% were bilaterally located. The Ashkenazi group showed a significant higher prevalence of commissural lip pits (19.4%) when compared to the prevalence in the Sephardic group (14.1%) and the Eastern group (21.1%).

Adolescent↗